Virtual screening, molecular simulations and bioassays: Discovering novel microsomal prostaglandin E Synthase-1 (mPGES-1) inhibitors.

Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible prostaglandin E synthase expressed following exposure to pro-inflammatory stimuli. The mPGES-1 enzyme represents a new target for the therapeutic treatment of acute and chronic inflammatory disorders and cancer. In the present study, compounds from the ZINC15 database with an indole scaffold were docked at the mPGES-1 binding site using Glide (high-throughput virtual screening [HTVS], standard precision [SP] and extra precision [XP]), and the stabilities of the complexes were determined by molecular simulation studies.

Discovery of novel and selective inhibitors targeting protein tyrosine phosphatase 1B (PTP1B): Virtual screening and molecular dynamic simulation.

Protein tyrosine phosphatase 1B (PTP1B) is a promising target for Type II diabetes, obesity, and cancer therapeutics. However, capturing selectivity over T cell protein tyrosine phosphatase (TCPTP) is key to PTP1B inhibitor discovery. Current studies demonstrate that the phosphotyrosine (pTyr) binding site confers selectivity to inhibitors.

Design, synthesis and antiproliferative activity evaluation of fluorine-containing chalcone derivatives.

A series of new chalcones containing fluoro atom at B ring have been designed, synthesized, and evaluated to be antiproliferative activity against a panel of human tumor cell lines. Some of the analogs (, , , , and ) displayed powerful antiproliferative effects to certain human tumor cells, but all of them were devoid of any cytotoxicity towards the normal HEK 293. Acridine orange staining data supported that the cytotoxic and antiproliferative effects of the synthesized analogs on tumor cells are mediated through apoptosis.

Synthesis, molecular modeling studies, ADME prediction of arachidonic acid carbamate derivatives, and evaluation of their acetylcholinesterase activity.

In this work, a series of novel anandamide units containing carbamate were designed and synthesized. All the derivatives were evaluated in vitro for their inhibitory potential against the electric eel acetylcholinesterase enzyme (AChE) and showed reversible inhibitions. The compounds 7a, 7d, 7e, and 7f are mixed inhibitors of AChE, while the compounds 7b, 7c, and 7g are uncompetitive (K in the range 0.

A Comparison of the Inhibitory Effects of Anti-Cancer Drugs on Thioredoxin Reductase and Glutathione S-Transferase in Rat Liver.

Background: While Thioredoxin Reductase (TrxR) plays an important role in regulation of the intracellular redox balance and various signalling pathways, Glutathione S-Transferase (GSTs) enzymes belong to the detoxification family that catalyse the conjugation of glutathione with various endogenous and xenobiotic electrophiles. Since TrxR and GSTs are overexpressed in many cancer cells, they have been identified as potential targets to develop chemotherapeutic strategies.

Method: The mitochondrial TrxR (TrxR2) enzyme and the cytosolic GST enzyme was purified from rat liver via affinity chromatography.

Efficient expression of recombinant human telomerase inhibitor 1 (hPinX1) in Pichia pastoris.

PinX1 encoded by a remarkable tumor suppressor gene and located in human chromosome 8p23 is known as telomerase inhibitor. In recent years, this protein has been of interest as clinically tumor suppressor. Pichia pastoris expression system is preferred to produce heterologous proteins and is suitable for industrial and research purposes.

Some indazoles reduced the activity of human serum paraoxonase 1, an antioxidant enzyme: inhibition and molecular modeling studies.

Paraoxonase 1 (PON1: EC 3.1.8.

Synthesis and biological evaluation of phloroglucinol derivatives possessing α-glycosidase, acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase inhibitory activity.

A series of novel phloroglucinol derivatives were designed, synthesized, characterized spectroscopically and tested for their inhibitory activity against selected metabolic enzymes, including α-glycosidase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human carbonic anhydrase I and II (hCA I and II). These compounds displayed nanomolar inhibition levels and showed K values of 1.14-3.

Synthesis and Carbonic Anhydrase Inhibition of Tetrabromo Chalcone Derivatives.

In the present study, human carbonic anhydrase (hCA) enzyme was purified and characterized from fresh blood human red cells by Sepharose-4B-l-tyrosine-sulfanilamide affinity gel chromatography. Secondly, a series of new tetrabromo chalcone derivatives containing 4,7-methanoisoindol-1,3-dione (2a-i) were synthesized from the addition of Br to related chalcone derivatives (1a-i). The structures of the new molecules (2a-i) were confirmed by means of H NMR, C NMR and elemental analysis.

Assessment of the inhibitory effects and molecular docking of some sulfonamides on human serum paraoxonase 1.

Paraoxonase-1 (PON1) is an organophosphate hydrolyzer and antiatherogenic enzyme. Due to the PON1's crucial functions, inhibitors and activators of PON1 must be known for pharmacological applications. In this study, we investigated the in vitro effects of some sulfonamides compounds on human serum PON1 (hPON1).